Increasing evidence suggests that morphological and functional neuronal rearrangements are partly responsible for the recovery of cerebral function after brain damage. The present proposal focusses on a neuronal rearrangement in the rat hippocampal formation which appears particular well-suited for the application of sensitive and specific biochemical techniques to characterizing and understanding the molecular basis of these rearrangements. Four weeks after a septal lesion, peripheral noradrenergic fibers appear in the rat dentate and hippocampal gyri. The hypothesis underlying this proposal is that these noradrenergic fibers are functionally replacing damaged cholinergic neurons in the septo-hippocampal pathway. In order to test this hypothesis, the adrenergic and cholinergic receptors of the rat hippocampal formation will be characterized using radioligand binding and other biochemical techniques. Receptor-mediated changes in hippocampal phospholipid metabolism will be identified and used as a measure of adrenergic and cholinergic responses both in vitro and in vivo. These biochemical studies will be correlated with appropriate anatomical controls during experimental manipulations that alter the appearance of the peripheral noradrenergic fibers. From these correlative observations, testable hypothesis about the molecular events that regulate this neuronal rearrangement or "neuronal sprouting" will be formulated. It is likely that some general principles about neuronal sprouting can be deduced from a careful study of this neuronal rearrangement. Hopefully, these sprouting catecholamine neutrons will prove a useful model for the recovery of cerebral function after stroke. In this way, the present proposal may contribute to the rational prediction of therapy for enhancing recovery after cerebral infarction.